Ignite Creation Date:
2024-05-05 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00059579
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2003-04-29
Brief Title:
Brain Regulation of Emotions in People With Depression and Anhedonia
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Functional MRI Study of Brain Mechanism Mediating Anhedonia in Major Depression
Status:
COMPLETED
Status Verified Date:
2010-11-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will use magnetic resonance imaging MRI to examine how the brain regulates emotions in healthy people and in patients who have major depression and anhedonia loss of feeling of pleasure in things that normally give pleasure
Healthy normal volunteers and patients between 18 and 50 years of age with major depression with or without significant anhedonia are eligible for this study Candidates will be screened with a psychiatric interview a physical examination that will include blood and urine samples and an electrocardiogram and a questionnaire about their emotions
Participants will perform a monetary reward task while lying in an MRI scanner The task is similar to playing a computer video game with the possibility of winning cash The amount of cash is largely dependent on the subjects performance The accumulated amount of cash earned in a session will fluctuate depending on the subjects continuing performance level That is during a single session a subject could lose money earned early in the session if his or her performance later in the session is not as good as earlier
MRI pictures will be taken during performance of the task MRI uses a magnetic field and radio waves to produce images of body tissues and organs The patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The procedure will last about 1 to 1-12 hours
Healthy normal volunteers and patients between 18 and 50 years of age with major depression with or without significant anhedonia are eligible for this study Candidates will be screened with a psychiatric interview a physical examination that will include blood and urine samples and an electrocardiogram and a questionnaire about their emotions
Participants will perform a monetary reward task while lying in an MRI scanner The task is similar to playing a computer video game with the possibility of winning cash The amount of cash is largely dependent on the subjects performance The accumulated amount of cash earned in a session will fluctuate depending on the subjects continuing performance level That is during a single session a subject could lose money earned early in the session if his or her performance later in the session is not as good as earlier
MRI pictures will be taken during performance of the task MRI uses a magnetic field and radio waves to produce images of body tissues and organs The patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The procedure will last about 1 to 1-12 hours
Detailed Description:
Anhedonia has been one of the two key diagnostic criteria for major depressive disorder MDD since the publication of The Diagnostic and Statistical Manual of Mental Disorders Third Edition yet little is known about its neural substrates Neuroimaging studies have identified numerous brain regions that are thought to be involved with MDD Most studies dealt with MDD as a syndromal entity and not surprisingly yielded quite variable results with respect to the areas of the brain identified the nature of the functional changes ie decrease or increase in activities lateralization and correlation with clinical symptoms Clinical heterogeneity and lack of symptom-specific targets are presumably among the factors contributing to the variability The hypothesis that a functionally impaired mesolimbic dopaminergic pathway may comprise a part of neural substrate underlying core MDD symptoms of anhedonia and loss of motivation has been proposed Nevertheless the roles of brain reward mechanisms in mediating anhedonia in MDD remain unclear Availability of appropriate experimental paradigms that can be used empirically to measure anhedonia is a prerequisite to test such a hypothesis Recent studies using monetary incentive paradigms coupled with neuroimaging techniques have identified hemodynamic responses in structures that serve as part of the mesolimbic dopaminergic pathway during processing rewards in healthy humans
We hypothesize that anhedonia in MDD is associated with impairment of brain reward mechanisms such that dysfunction of the orbital and ventromedial frontal cortices involved in the impaired hedonic attribution capacity while dysfunction of the ventral striatum area that contains the nucleus accumbens is involved with the reduced or lack of reactivity to rewarding environmental stimuli in patients with MDD Our hypothesis is to link specific neural substrates to the two psychiatric components of anhedonia ie loss of interest and lack of reactivity as defined in the diagnostic criteria for MDD We plan to operationally test our hypothesis by using empirical measurement of reward responses in MDD patients with and without significant anhedonia using a conditioning task assessing appetitive and aversive learning without any performance aspects and spatial delayed response task assessing the relationship between reward performance and mood with the event-related functional magnetic resonance imaging method We expect to find reduced activation of the ventral striatum orbital and ventromedial frontal cortices in response to monetary incentive stimuli in MDD patients with significant anhedonia relative to MDD patients without anhedonia and healthy control
In order to assess the role of dopamine in anhedonia and in reward processing we propose to assess the effect of dietary tyrosine plus phenylalanine depletion on the neural and behavioral responses associated with the performing of the monetary reward tasks investigated herein in an additional sample of subjects Dietary depletion of tyrosine and phenylalanine two DA precursors is a validated method to induce significant reduction of the brain DA concentration as shown in two previous 11CRaclopride PET studies We hypothesize that depressed patients will show less activation than controls in brain regions associated with the mesolimbic DA system such as striatum amygdala anterior cingulate gyrus and orbitofrontal cortex in response to reward in the placebo condition We expect tyrosine and phenylalanine depletion to induce a similar neural impairment to reward in healthy subjects including a reduction of the neural activation in the striatum amygdala anterior cingulate gyrus and orbitofrontal cortex in response to reward The reduction of the neural activation in those regions will be stronger in healthy controls than in depressed patients Finally we hypothesize that tyrosine depletion will influence negatively the valence ratings of rewarding stimuli in healthy subjects In depressed patients anhedonia scores will correlate negatively with the valence ratings of rewarding stimuli in the placebo condition already
The outcome of the proposed work may provide clues for diagnosis classification and treatment of MDD and may also yield leads for identifying the fundamental neural mechanisms underlying anhedonia in other disabling psychiatric conditions such as schizophrenia and addiction
We hypothesize that anhedonia in MDD is associated with impairment of brain reward mechanisms such that dysfunction of the orbital and ventromedial frontal cortices involved in the impaired hedonic attribution capacity while dysfunction of the ventral striatum area that contains the nucleus accumbens is involved with the reduced or lack of reactivity to rewarding environmental stimuli in patients with MDD Our hypothesis is to link specific neural substrates to the two psychiatric components of anhedonia ie loss of interest and lack of reactivity as defined in the diagnostic criteria for MDD We plan to operationally test our hypothesis by using empirical measurement of reward responses in MDD patients with and without significant anhedonia using a conditioning task assessing appetitive and aversive learning without any performance aspects and spatial delayed response task assessing the relationship between reward performance and mood with the event-related functional magnetic resonance imaging method We expect to find reduced activation of the ventral striatum orbital and ventromedial frontal cortices in response to monetary incentive stimuli in MDD patients with significant anhedonia relative to MDD patients without anhedonia and healthy control
In order to assess the role of dopamine in anhedonia and in reward processing we propose to assess the effect of dietary tyrosine plus phenylalanine depletion on the neural and behavioral responses associated with the performing of the monetary reward tasks investigated herein in an additional sample of subjects Dietary depletion of tyrosine and phenylalanine two DA precursors is a validated method to induce significant reduction of the brain DA concentration as shown in two previous 11CRaclopride PET studies We hypothesize that depressed patients will show less activation than controls in brain regions associated with the mesolimbic DA system such as striatum amygdala anterior cingulate gyrus and orbitofrontal cortex in response to reward in the placebo condition We expect tyrosine and phenylalanine depletion to induce a similar neural impairment to reward in healthy subjects including a reduction of the neural activation in the striatum amygdala anterior cingulate gyrus and orbitofrontal cortex in response to reward The reduction of the neural activation in those regions will be stronger in healthy controls than in depressed patients Finally we hypothesize that tyrosine depletion will influence negatively the valence ratings of rewarding stimuli in healthy subjects In depressed patients anhedonia scores will correlate negatively with the valence ratings of rewarding stimuli in the placebo condition already
The outcome of the proposed work may provide clues for diagnosis classification and treatment of MDD and may also yield leads for identifying the fundamental neural mechanisms underlying anhedonia in other disabling psychiatric conditions such as schizophrenia and addiction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-M-0149 | None | None | None |